After studying this chapter you should understand:
The physiology of the natural anticoagulant mechanisms and how they limit the generation of activated enzymes in the coagulation cascade.
How genetic defects in natural anticoagulant mechanisms and abnormalities in procoagulant factors can predispose to venous thrombosis.
The interaction of acquired and genetic risk factors in the pathogenesis of venous thrombosis.
As mentioned in the introduction to this section of the book, thrombosis plays a commanding role as a complication of highly prevalent disorders such as obesity, diabetes, and cancer. Myocardial infarction is the leading cause of mortality from arterial thrombosis, whereas pulmonary embolus accounts for most deaths due to venous thrombosis. In this chapter, we will stress the pathophysiologic principles underlying in vivo thrombus formation and the acquired and inherited factors that put patients at increased risk.
Insight into the pathogenesis of thrombotic disorders began with the 19th century pathologist Rudolf Virchow, whose clinical and postmortem observations led him to postulate that the formation of blot clots sufficiently large to occlude major blood vessels was dependent upon three independent processes:
Abnormal blood flow—principally stasis.
Irritation of the vessel wall due to trauma, or a degenerative/inflammatory process such as atherosclerosis.
Enhanced blood coagulation, or what we now call hypercoagulability.
Virchow's triad provides a useful framework for evaluating any patient who has developed clinically significant thrombotic disease. The history will often reveal factors that predispose to stasis, such as immobilization of a limb, pregnancy, or prolonged inactivity. Further studies may identify a specific type of vascular pathology as well as abnormalities in blood coagulation. In this chapter, venous thrombosis will be covered in more depth than arterial thrombosis because the former is closely linked to well-defined abnormalities in coagulation, whereas the latter is much more dependent on vascular abnormalities, particularly atherosclerosis, which lie outside the scope of this book.
As outlined in Table 17-1, both nature and nurture contribute to the development of venous thrombosis. As listed in the left hand column, a wide spectrum of acquired or secondary factors puts individuals at increased risk. Several, such as increasing age, male sex, and obesity, are weak but statistically significant risk factors. In contrast, a history of venous thrombosis is a strong predictor of repeated episodes. Immobilization due to extended bed rest or prolonged air travel leads to blood stasis, particularly in the lower extremities. Immobilization is also an important contributor to the increased risk of venous thrombosis in patients recovering from major surgery. Pregnancy causes stasis in the legs, owing to impairment of venous return by the enlarging uterus. Malignancy and estrogen use will be discussed later in the chapter along with other less common acquired risk factors.
TABLE 17-1Risk Factors for Venous Thrombosis
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